MECHANISMS OF REACTIONS OF OXYGEN WITH HEME PROTEINS

氧与血红素蛋白的反应机制

• 批准号: 3334665
• 负责人: TEDDY G. TRAYLOR
• 金额: $ 17.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-02-01 至 1992-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3334665
• 关键词: carbon monoxide; chemical binding; chemical models; chemical reaction; chemical structure function; chromatography; computer simulation; conformation; cyanides; electron transport; heme; hemoglobin; hemoprotein; hemoprotein structure; infrared spectrometry; ligands; molecular site; myoglobin; nuclear magnetic resonance spectroscopy; porphyrins; respiratory oxygen

Model compounds for hemoglobin and related hemoproteins will be prepared and the effect of their structure on the dynamics of reaction with dioxygen, carbon monoxide, and isonitriles studied. Geminate recombination of isocyanides, nitric oxide and dioxygen to various model compounds for R- and T-state hemoglobins and hemes with different extents of steric, electronic and polar effects at the site will be studied using femptosecond, picosecond, and nanosecond kinetic methods. Photolysis quantum yields will be determined for correlation with the kinetic studies. Special efforts will be made to determine relative rates of binding and conformational change in both the heme cyclophanes and in heme proteins. New compounds will be designed to explore the effects of porphyrin flexibility, distortion of "stiffness" upon dioxygen and other ligand binding. Cooperatively binding heme compounds now in hand and newly designed systems will be studied with regard to kinetics and equilibria of carbon monoxide and dioxygen binding in order to mimic the cooperativity in hemoglobin. This study will define those characteristics of heme compounds and their environment which control the varied reactivities of such hemes in hemoproteins. This information will provide the means of understanding the cooperativity in hemoglobin, the conformational changes in proteins, and other effects which govern ligand affinity. The cyclophane porphyrins and the dimer heme compounds will also be used to probe the effect of intervening molecular structure on porphyrin-to-porphyrin electron transfer.

将制备血红蛋白和相关血红蛋白的模型化合物 以及它们的结构对反应动力学的影响 研究了氧气、一氧化碳和异腈。双子复合 将异氰化物、一氧化氮和氧气转化为各种R- 以及具有不同立体程度的T-态血红蛋白和血红素， 现场的电子效应和极性效应将用 飞秒、皮秒和纳秒动力学方法。光解 量子产率将被确定为与动力学相关 学习。将作出特别努力，以确定 环状亚铁血红素和亚铁血红素的结合和构象变化 蛋白质。将设计新的化合物来探索 卟啉的柔韧性、氧的“僵硬”变形和其他 配基结合。合作结合的血红素化合物现在手中和新的 所设计的系统将从动力学和平衡性方面进行研究 一氧化碳和氧气的结合，以模拟 血红蛋白。 这项研究将确定血红素化合物的这些特征及其 控制这些血红素在体内的各种反应性的环境 血球蛋白。这些信息将提供了解 血红蛋白的协作性，蛋白质的构象变化，以及 其他影响配基亲和力的因素。 环状卟啉和二聚体血红素化合物也将被用于 探讨介入性分子结构对分子质量的影响 卟啉对卟啉的电子转移。